ES2772689T3 - Derivado de oxa espiro, método de preparación del mismo y aplicaciones del mismo en medicamentos - Google Patents

Derivado de oxa espiro, método de preparación del mismo y aplicaciones del mismo en medicamentos Download PDF

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Publication number: ES2772689T3
Authority: ES; Spain
Prior art keywords: cycloalkyl; heterocyclyl; alkyl; group; heteroaryl
Prior art date: 2015-10-15
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Active

Application number

ES16854888T

Other languages

English (en)

Spanish (es)

Inventor

Xin Li

Binqiang Feng

Yang Chen

Tao Liu

Feng He

Mingxun He

Weikang Tao

Piaoyang Sun

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Jiangsu Hengrui Medicine Co Ltd

Shanghai Hengrui Pharmaceutical Co Ltd

Original Assignee

Jiangsu Hengrui Medicine Co Ltd

Shanghai Hengrui Pharmaceutical Co Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2015-10-15

Filing date

2016-09-30

Publication date

2020-07-08

2016-09-30 Application filed by Jiangsu Hengrui Medicine Co Ltd, Shanghai Hengrui Pharmaceutical Co Ltd filed Critical Jiangsu Hengrui Medicine Co Ltd

2020-07-08 Application granted granted Critical

2020-07-08 Publication of ES2772689T3 publication Critical patent/ES2772689T3/es

Status Active legal-status Critical Current

2036-09-30 Anticipated expiration legal-status Critical

Links

238000002360 preparation method Methods 0.000 title claims description 9
239000003814 drug Substances 0.000 title description 16
229940079593 drug Drugs 0.000 title description 11
125000003003 spiro group Chemical group 0.000 title description 6
150000001875 compounds Chemical class 0.000 claims abstract description 145
-1 nitro, hydroxy Chemical group 0.000 claims abstract description 117
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 113
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 108
125000000217 alkyl group Chemical group 0.000 claims abstract description 93
239000000203 mixture Substances 0.000 claims abstract description 92
125000003118 aryl group Chemical group 0.000 claims abstract description 75
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 73
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229910052736 halogen Inorganic materials 0.000 claims abstract description 46
150000002367 halogens Chemical group 0.000 claims abstract description 46
150000003839 salts Chemical class 0.000 claims abstract description 38
125000001188 haloalkyl group Chemical group 0.000 claims abstract description 34
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 32
125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 31
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229910052739 hydrogen Inorganic materials 0.000 claims abstract description 28
239000001257 hydrogen Substances 0.000 claims abstract description 28
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125000004438 haloalkoxy group Chemical group 0.000 claims abstract description 16
125000003342 alkenyl group Chemical group 0.000 claims abstract description 15
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 15
125000004043 oxo group Chemical group O=* 0.000 claims abstract description 8
229910052805 deuterium Inorganic materials 0.000 claims abstract description 6
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims abstract description 5
238000000034 method Methods 0.000 claims description 32
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 26
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208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
239000000546 pharmaceutical excipient Substances 0.000 claims description 7
238000006268 reductive amination reaction Methods 0.000 claims description 7
201000010099 disease Diseases 0.000 claims description 6
206010028980 Neoplasm Diseases 0.000 claims description 4
206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
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208000025966 Neurological disease Diseases 0.000 claims description 3
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YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 135
238000006243 chemical reaction Methods 0.000 description 103
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230000002829 reductive effect Effects 0.000 description 67
238000004949 mass spectrometry Methods 0.000 description 61
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
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238000010828 elution Methods 0.000 description 43
238000004809 thin layer chromatography Methods 0.000 description 42
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 40
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210000004027 cell Anatomy 0.000 description 21
239000003921 oil Substances 0.000 description 21
235000019198 oils Nutrition 0.000 description 21
239000000706 filtrate Substances 0.000 description 19
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125000001424 substituent group Chemical group 0.000 description 16
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 15
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238000002474 experimental method Methods 0.000 description 14
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NVGSPCSQFOQQPW-OAHLLOKOSA-N 2-[(9r)-9-pyridin-2-yl-6-oxaspiro[4.5]decan-9-yl]acetaldehyde Chemical compound C([C@@](C1)(CC=O)C=2N=CC=CC=2)COC21CCCC2 NVGSPCSQFOQQPW-OAHLLOKOSA-N 0.000 description 12
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HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
125000002619 bicyclic group Chemical group 0.000 description 12
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
125000003367 polycyclic group Chemical group 0.000 description 11
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 11
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125000005842 heteroatom Chemical group 0.000 description 10
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LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
239000000556 agonist Substances 0.000 description 9
125000004429 atom Chemical group 0.000 description 9
229960005181 morphine Drugs 0.000 description 9
125000006413 ring segment Chemical group 0.000 description 9
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 8
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108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 8
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
0 B[C@](*)(CC[C@]1*(CC*2CC3(CCCC3)OCC2)=C)CCc2c1cc*(*)c2 Chemical compound B[C@](*)(CC[C@]1*(CC*2CC3(CCCC3)OCC2)=C)CCc2c1cc*(*)c2 0.000 description 7
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125000003282 alkyl amino group Chemical group 0.000 description 7
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IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
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CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical group C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
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230000001225 therapeutic effect Effects 0.000 description 1
238000011285 therapeutic regimen Methods 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
230000026683 transduction Effects 0.000 description 1
238000010361 transduction Methods 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
239000012588 trypsin Substances 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
239000003643 water by type Substances 0.000 description 1
229940045860 white wax Drugs 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4433—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4436—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Epidemiology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

ES16854888T 2015-10-15 2016-09-30 Derivado de oxa espiro, método de preparación del mismo y aplicaciones del mismo en medicamentos Active ES2772689T3 (es)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
CN201510665328		2015-10-15
CN201511032876		2015-12-31
PCT/CN2016/101064 WO2017063509A1 (fr)	2015-10-15	2016-09-30	Dérivé oxa spiro, son procédé de préparation, et ses applications dans des médicaments

Publications (1)

Publication Number	Publication Date
ES2772689T3 true ES2772689T3 (es)	2020-07-08

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ID=58517778

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Application Number	Title	Priority Date	Filing Date
ES16854888T Active ES2772689T3 (es)	2015-10-15	2016-09-30	Derivado de oxa espiro, método de preparación del mismo y aplicaciones del mismo en medicamentos

Country Status (16)

Country	Link
US (1)	US10442793B2 (fr)
EP (1)	EP3354649B1 (fr)
JP (1)	JP6824502B2 (fr)
KR (1)	KR102703513B1 (fr)
CN (1)	CN107001347B (fr)
AU (1)	AU2016339404B2 (fr)
CA (1)	CA3000761C (fr)
DK (1)	DK3354649T3 (fr)
ES (1)	ES2772689T3 (fr)
HU (1)	HUE048032T2 (fr)
MX (1)	MX382815B (fr)
PL (1)	PL3354649T3 (fr)
PT (1)	PT3354649T (fr)
RU (1)	RU2733373C2 (fr)
TW (1)	TWI727981B (fr)
WO (1)	WO2017063509A1 (fr)

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CN112638906B (zh) *	2018-10-12	2022-05-27	江苏恒瑞医药股份有限公司	一种阿片样物质受体(mor)激动剂的结晶形式及制备方法
CN112638907B (zh) *	2018-10-12	2022-04-12	江苏恒瑞医药股份有限公司	一种阿片样物质受体(mor)激动剂的结晶形式及制备方法
WO2020147848A1 (fr) *	2019-01-17	2020-07-23	上海海雁医药科技有限公司	Dérivé d'oxaspiro substitué tricyclique, son procédé de préparation et son utilisation pharmaceutique
CN111662284B (zh) *	2019-03-06	2021-08-10	上海海雁医药科技有限公司	双杂环取代的氧杂螺环衍生物、其制法与医药上的用途
WO2021027304A1 (fr) *	2019-08-14	2021-02-18	上海海雁医药科技有限公司	Composé analgésique, son procédé de préparation et son utilisation pharmaceutique
CN113412263B (zh) *	2020-01-17	2024-07-26	上海海雁医药科技有限公司	氮杂双环取代的氧杂螺环衍生物、其制法与医药上的用途
EP4092032A4 (fr)	2020-01-17	2024-02-28	Shanghai Haiyan Pharmaceutical Technology Co., Ltd.	Dérivé de pyrrolopyrazole oxaspiro-substitué optiquement pur, son procédé de préparation et son utilisation pharmaceutique
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JP7751645B2 (ja)	2020-12-29	2025-10-08	上海海雁医薬科技有限公司	オキシスピロ環置換ピロロピラゾール誘導体及びその中間体並びにその調製方法
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2016
- 2016-09-30 HU HUE16854888A patent/HUE048032T2/hu unknown
- 2016-09-30 EP EP16854888.1A patent/EP3354649B1/fr active Active
- 2016-09-30 PL PL16854888T patent/PL3354649T3/pl unknown
- 2016-09-30 RU RU2018115569A patent/RU2733373C2/ru active
- 2016-09-30 AU AU2016339404A patent/AU2016339404B2/en active Active
- 2016-09-30 KR KR1020187012600A patent/KR102703513B1/ko active Active
- 2016-09-30 MX MX2018004175A patent/MX382815B/es unknown
- 2016-09-30 CN CN201680003945.6A patent/CN107001347B/zh active Active
- 2016-09-30 ES ES16854888T patent/ES2772689T3/es active Active
- 2016-09-30 CA CA3000761A patent/CA3000761C/fr active Active
- 2016-09-30 WO PCT/CN2016/101064 patent/WO2017063509A1/fr not_active Ceased
- 2016-09-30 JP JP2018515975A patent/JP6824502B2/ja active Active
- 2016-09-30 PT PT168548881T patent/PT3354649T/pt unknown
- 2016-09-30 DK DK16854888.1T patent/DK3354649T3/da active
- 2016-09-30 US US15/766,985 patent/US10442793B2/en active Active
- 2016-10-14 TW TW105133229A patent/TWI727981B/zh active

Also Published As

Publication number	Publication date
EP3354649B1 (fr)	2019-12-04
HUE048032T2 (hu)	2020-05-28
RU2018115569A3 (fr)	2020-01-20
PL3354649T3 (pl)	2020-07-27
CA3000761C (fr)	2024-02-13
JP6824502B2 (ja)	2021-02-03
CN107001347A (zh)	2017-08-01
KR20180063251A (ko)	2018-06-11
EP3354649A1 (fr)	2018-08-01
RU2733373C2 (ru)	2020-10-01
US10442793B2 (en)	2019-10-15
EP3354649A4 (fr)	2018-08-08
CA3000761A1 (fr)	2017-04-20
AU2016339404B2 (en)	2020-08-27
US20180297988A1 (en)	2018-10-18
TWI727981B (zh)	2021-05-21
DK3354649T3 (da)	2020-02-24
KR102703513B1 (ko)	2024-09-06
TW201718558A (zh)	2017-06-01
PT3354649T (pt)	2020-02-03
MX382815B (es)	2025-03-12
BR112018006448A2 (pt)	2018-10-16
JP2018534257A (ja)	2018-11-22
CN107001347B (zh)	2019-09-24
WO2017063509A1 (fr)	2017-04-20
AU2016339404A1 (en)	2018-05-24
MX2018004175A (es)	2018-06-06
RU2018115569A (ru)	2019-11-18

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